Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The approximate association constants of the plasma vitamin D binding globulin (Gc-globulin) for 25-hydroxycholecalciferol (25(OH)D3) and the plasma 25(OH)D3 binding capacities were measured in samples from 123 patients with a variety of disorders. No gross differences in binding affinities were observed between different groups of patients and controls. Many patients, however, had moderately reduced, and several had grossly reduced, plasma binding capacities. The changes in Gc-globulin relative to some other proteins are also described in detail in three patients during the course of their illness. Gc-globulin concentration and hence plasma vitamin D binding capacity can undergo rapid and marked changes during illness.
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PMID:Vitamin D binding globulin levels and affinity in various clinical conditions. 689 97

Group-specific component (vitamin D-binding protein) was purified to homogeneity from human plasma by a three-step procedure involving pseudo-ligand affinity chromatography on immobilized Cibacron blue F3-GA followed by gel filtration and ion-exchange chromatography. Upon pseudo-ligand chromatography, Gc globulin was separated into two peaks. The first, which represented approx. 4% of the total Gc globulin, was eluted together with other alpha-globulins of similar Mr and/or pI, and the second (96% of Gc globulin) was clearly retarded. Collection of the latter provided a fraction 10-fold enriched in Gc globulin, with yields higher than 90%. Incubation of plasma with trace amounts of radioactively-labeled 25-OH vitamin D3 showed that the radioactivity coeluted with the first peak. In addition, after saturation with 25-OH vitamin D3, all the Gc globulin was eluted in the first peak. This indicates that the two peaks correspond to the holo and the apo forms of the protein, respectively, and suggests that either the interaction of the apo form with the Cibacron blue dye involves the binding site for vitamin D metabolites, or that the holo-protein undergoes a conformational change as a consequence of formation of the complex.
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PMID:Interaction of group-specific component (vitamin D-binding protein) with immobilized Cibacron blue F3-GA. 689 18

1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) has been shown to modulate lymphocyte activation in vitro. Through binding to specific receptors 1,25-(OH)2 D3 inhibits proliferation, immunoglobulin production and the release of cytokines. Moreover, 1,25-(OH)2 D3 is efficiently produced by activated monocytes. These findings suggest that 1,25-(OH)2 D3 may play a role as a regulator of immunological activation. Consequently, we found it of interest to study the serum levels of the two major metabolites of vitamin D3 in patients with systemic lupus erythematosus (SLE) (n = 21), rheumatoid arthritis (RA) (n = 29) and osteoarthritis (n = 12). In patients with SLE the levels of 25-OH D3 were below those of the healthy controls (p = 0.0008) and OA (p = 0.0168). The levels 1,25-(OH)2 D3 corresponded to normal levels. There were no significant correlations between 25-OH D3 levels and clinical or paraclinical disease manifestations. Further, the phenotypic distribution of Gc-globulin, which binds vitamin D3 metabolites in circulation, was normal. The serum concentrations of 1,25-(OH)2 D3 and 25-OH D3 in patients with RA and OA corresponded to those of the controls. Although the cause of the reduced 25-OH D3 levels in SLE patients is unclear, possible beneficial effects of administration of vitamin D to these patients should be considered.
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PMID:Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus. 758 74

The transporter of vitamin D and its metabolites in blood has received increasing attention in recent years, and is recognized to be a member of a gene family that includes albumin and alpha-fetoprotein. Identical to the group specific component (Gc-globulin) of serum, the protein is a single-chain polypeptide constitutively synthesized in liver that circulates in amounts in far excess of normal vitamin D metabolite concentrations in blood. It plays the major role in the egress of endogenously synthesized vitamin D, from skin and appears to restrain D-sterols from too rapid/excessive cell entry. Along with plasma gelsolin, it comprises the plasma actin-scavenger system that facilitates removal of actin, liberated from lysed cells, by depolymerization and prevention of polymerization. Recently, the protein has been shown to behave as a co-chemotaxin specific for the complement peptide C5a, and its sialic acid-free form has been reported to play a role in macrophage activation. The latter functions strongly implicate its participation in inflammation responses. A unifying hypothesis might also suggest the protein to provide focal D-sterol delivery to cells that are important to the resolution of tissue injuries.
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PMID:Plasma vitamin D-binding protein (Gc-globulin): multiple tasks. 762 13

Vitamin D-binding protein (DBP), a multifunctional, highly polymorphic glycoprotein responsible for the transport of vitamin D and for sequestering extracellular actin, was isolated from human serum and crystallized using vapour diffusion methods. The crystals were grown from 7.5% v/v polyethylene glycol 400 and 0.1 M acetate buffer at pH 4.6. These crystals show diffraction patterns consistent with the tetragonal space groups P4(1) and P4(3) with unit cell dimensions a = b = 135.5(4) A and c = 75.9(4) A. They diffract to 2.3 A. Using polyacrylamide gel electrophoresis it was shown that according to their electrophoretic mobility the O-glycosylated isoforms, with a terminal sialic acid residue, are absent in the crystals.
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PMID:Crystallization and X-ray investigation of vitamin D-binding protein from human serum. Identification of the crystal content. 763 9

A well defined polymorphism of vitamin D-binding/group-specific component (GC) residues in exon 11. To characterize the molecular basis of GC*1A2 and GC*1A3, common in some Asian populations, we analyzed all coding exons amplified by the polymerase chain reaction. GC*1F was divided into GC*1FC and GC*1FT by a C-T transition in the third nucleotide of the codon (TGC/T) for cysteine283 in exon 8. The sequencing of exons 8 and 11 showed that GC*1A2 and GC*1A3 had occurred on a GC*1FC genetic background. They also shared a substitution of cysteine (TGC) for arginine (CGC) at position 429 in exon 11. GC*1A2 was characterized by having glycine (GGC) instead of serine (AGC) at position 335 in exon 9. GC*1A2 evolved from GC*1FT by three mutational events, i.e. GC*1FT-->GC*1FC-->GC*1A3-->GC*1A2. No evidence was obtained for the existence of the duplicated gene GC*1F.1A2 suggested by isoelectric focusing (IEF) of serum samples. The idea that the characteristic banding pattern of GC*1F.1A2 after IEF results from partial formation of a disulfide bond in the additional cysteine at position 429 is discussed.
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PMID:Characterization of mutants of the vitamin D-binding protein/group-specific component: molecular evolution of GC*1A2 and GC*1A3, common in some Asian populations. 775 70

Vitamin D-binding protein (DBP) is primarily involved in the binding and transportation of vitamin D3 and its various metabolites to target organs and tissues. This is manifested by the ability of DBP to bind vitamin D3 and its metabolites with high affinity. In the present study we developed 25-hydroxyvitamin D3-3 beta-(1,2-epoxypropyl)ether (25-OH-D3-epoxide) as an affinity labeling reagent of human DBP (hDBP). Competitive radioligand binding assays of 25-OH-D3-epoxide with hDBP demonstrated that the binding affinity of this analog was similar to that of 25-hydroxyvitamin D3 (25-OH-D3). Incubation of 25-hydroxy[26(27)-3H]-vitamin D3-3 beta-(1,2-epoxypropyl)ether [[3H]25-OH-D3-epoxide] with hDBP covalently labeled the protein. When the incubation was carried out in the presence of a large excess of 25-OH-D3, labeling was removed completely. When human Cohn IV fraction, containing hDBP, was incubated with [3H]25-OH-D3-epoxide a single protein band, corresponding to hDBP, was labeled. Labeling was completely obliterated in the presence of a large amount of 25-OH-D3. However, an equivalent amount of 7-dehydrocholesterol had no effect on labeling. These results demonstrated that [3H]25-OH-D3-epoxide most probably labeled the vitamin D sterol-binding domain of hDBP.
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PMID:25-Hydroxy[26,27-methyl-3H]vitamin D3-3 beta-(1,2-epoxypropyl)ether: an affinity labeling reagent for human vitamin D-binding protein. 778 34

Serum vitamin D binding protein (DBP, also known as Gc-globulin) is a multifunctional protein capable of binding both vitamin D metabolites and actin. DBP can be visualized when analyzed by polyacrylamide gel electrophoresis followed by staining. Confirmation of its identity had previously required immunoprecipitation with specific anti-DBP antisera or occupancy of the protein with radioactive vitamin D sterols. We present studies showing that preincubation of G-actin with mammalian sera produced a discernible DBP protein band shift on native gel electrophoresis. Addition of DNaseI, a 33-kDa intracellular protein with an avid actin-binding site, to the incubations resulted in a supershift of DBP-actin complexes to an even more cathodal region of the gels. Following incubations with human, rat, and murine sera the same actin shift occurred as did the actin plus DNaseI supershift. The migrations of each complex were correlated with purified DBP migrations under identical conditions. It was confirmed that the supershifted bands contained DBP by Western blotting and detection of DBP by binding of 25-OH[3H]D3. After intravenous G-actin injections into living mice, a serum DBP-actin complex could be detected on native gels as the uncomplexed DBP band decreased in intensity. This simple, direct-staining technique appears to be suitable for identifying DBP/Gc phenotypes in human populations as well as for semiquantitatively monitoring the plasma actin-scavenger system in vivo in animal models or in human diseases.
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PMID:Electrophoretic mobility shift assay identifies vitamin D binding protein (Gc-globulin) in human, rat, and mouse sera. 866 May 73

Vitamin D-binding protein (DBP)/Gc-globulin, the major carrier of vitamin D and its metabolites in blood, is synthesized predominantly in the liver in a developmentally regulated fashion. By transient transfection analysis, we identified three regions in the 5'-flanking region of the rat DBP gene, segments F-2, B, and A, that contain tissue-specific transcriptional determinants. Gel mobility shift and DNase I footprinting analyses showed that all three regions contained binding sites for the hepatocyte nuclear factor 1 (HNF1), a transcriptional regulator composed of HNF1alpha and HNF1beta hetero- and homodimers. The activity of the most proximal segment A (coordinates -141 to -43) was DBP promoter-specific, position-dependent, and positively controlled by HNF1alpha. In contrast, the two more distal determinants (segments F-2 and B; coordinates -1844 to -1621 and -254 to -140, respectively) acted as classical enhancers in transfected hepatocyte-derived HepG2 cells; their activities were promoter- and orientation-independent, and disruption of their respective HNF1-binding sites resulted in marked loss of DBP gene expression. Remarkably, the activities of these two distal elements depended upon the relative levels of HNF1alpha and HNF1beta; HNF1alpha had a major stimulatory effect, whereas HNF1beta acted as a trans-dominant inhibitor of HNF1alpha-mediated enhancer activity. These results suggested that the net expression of the DBP gene reflected a balance between the two major HNF1 species; the relative abundance of HNF1alpha and HNF1beta proteins in a cell may thus play a critical role in determining the pattern of gene expression.
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PMID:Vitamin D-binding protein gene transcription is regulated by the relative abundance of hepatocyte nuclear factors 1alpha and 1beta. 977 68

Vitamin D-binding protein (DBP) is the major transport protein for the vitamin D sterols in a variety of mammalian and avian species. The DBP found in the emydid family of turtles is unique in that it exhibits high-affinity binding of both vitamin D and thyroxine (D/TBP). Sequence analysis has revealed that the emydid D/TBP is homologous to mammalian DBP and shares no homology with mammalian thyroxine-binding globulins. Northern blot analysis was used to examine the spatial profile of D/TBP transcription in the turtle Trachemys scripta. In both adults and hatchlings, two transcripts--the expected 1.5-kb full-length transcript and a second 0.8-kb transcript--were present in nearly all of the tissues examined. In adults, highest expression of the 1.5-kb transcript was seen in the kidney, gonad, and spleen, with lower levels in the liver and lung and no transcripts in skeletal muscle. In hatchlings, the full-length transcript was detected in a variety of tissues at similar levels. Injection of hatchlings with thyroxine increased levels of circulating D/TBP and transcript levels. These data are in marked contrast to observations in mammals in which transcription of DBP is confined predominantly to the liver. Further, the increase in circulating D/TBP associated with increased thyroidal activity may result from a direct or indirect activation of D/TBP transcription by thyroxine.
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PMID:Widespread expression of the mRNA encoding a novel vitamin D/thyroxine dual binding protein in the turtle Trachemys scripta. 1089 May 74


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